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Hafnium-based nanomaterials (Hf-NMs) have attracted the interest of numerous biomedical researchers by their unique properties. Recent years have witnessed significant advancements in the field of Hafnium-based nanomaterials, particularly in the context of cancer diagnosis and treatment. However, research in this area, especially concerning the clinical application of Hafnium-based nanomaterials, has not been thoroughly reviewed. This review will cover: 1) Classification and synthesis of Hafnium-based nanomaterials including Hafnium oxide nanomaterials, Hafnium Metal-Organic Frameworks/nanoscale coordination polymers (MOFs/NCPs); 2) Hafnium-based nanomaterials act as contrast enhancement agent for cancer imaging, and hafnium-based nanomaterials used for diagnosis in cancer liquid biopsy; 3) hafnium-based nanomaterials for cancer therapy, including hafnium-based nanomaterials for radiotherapy, hafnium-based nanomaterials for photodynamic therapy, hafnium-based nanomaterials for various combined therapy; and 4) Translation, toxicity, and safety for Hf-NMs in human and preclinical animal models. More attention will be given to the clinical translation of Hf-NMs in cancer. [ABSTRACT FROM AUTHOR]

The less invasive surfactant application (LISA) technology has been widely used to manage breathing in premature infants. Premature infants with respiratory distress syndrome (RDS) were retrospectively analyzed and divided into 2 groups according to the drug delivery methods used: LISA versus traditional pulmonary surfactant injection (INSURE). The decrease of transcutaneous saturation (TcSO2) and heart rate during surfactant delivery in the LISA group was higher than that in the INSURE group (P <.05). Between the 2 groups, there was no significant difference in the change in partial pressure of oxygen/fraction of inspired oxygen value before and after drug delivery; second-use pulmonary surfactant; noninvasive ventilation (NIV) failure rate; incidence of some complications; duration of NIV use; hospitalization time; and mortality (P >.05). However, the incidence of bronchopulmonary dysplasia (BPD) in the LISA group was lower than that in the INSURE group (P <.05). The clinical efficacy of LISA combined with the NIV treatment in premature infants with RDS was clear, and this treatment could reduce the incidence of BPD. [ABSTRACT FROM AUTHOR]

Product matching aims to identify identical or similar products sold on different platforms. By building knowledge graphs (KGs), the product matching problem can be converted to the Entity Alignment (EA) task, which aims to discover the equivalent entities from diverse KGs. The existing EA methods inadequately utilize both attribute triples and relation triples simultaneously, especially the interactions between them. This paper introduces a two-stage pipeline consisting of rough filter and fine filter to match products from eBay and Amazon. For fine filtering, a new framework for Entity Alignment, R elation-aware and A ttribute-aware Graph Attention Networks for E ntity A lignment (RAEA), is employed. RAEA focuses on the interactions between attribute triples and relation triples, where the entity representation aggregates the alignment signals from attributes and relations with Attribute-aware Entity Encoder and Relation-aware Graph Attention Networks. The experimental results indicate that the RAEA model achieves significant improvements over 12 baselines on EA task in the cross-lingual dataset DBP15K (6.59% on average Hits@1) and delivers competitive results in the monolingual dataset DWY100K. The source code for experiments on DBP15K and DWY100K is available at github (https://github.com/Mockingjay-liu/RAEA-model-for-Entity-Alignment). [ABSTRACT FROM AUTHOR]

To achieve carbon neutrality, it is necessary to grasp the essence of carbon neutrality. This paper looks into a few fundamental issues of carbon neutrality, and provides an in-depth analysis from the perspectives of environmental sustainability, technological innovation, economic viability, energy security, and international cooperation. It is shown that efforts for carbon neutrality need to focus on the key carbon dioxide (CO2) emissions from fossil fuel combustion. Fossil energy is considered to play a role as a short-term "ballast stone", but its attributes decide that it can hardly lead to a sustainable future, and its phasing-out is inevitable. Disruptive zero-carbon energy production and revolutionary technological innovation in its consumption are accelerating that phasing-out process; the zero-carbon-oriented carbon neutrality goal is growing more resilient to market headwinds and releasing momentum for high-quality development. Carbon capture and carbon sinks are indispensable, but they are unable to provide a satisfactory path to carbon neutrality. Carbon neutrality requires substantial capital investment, which can be provided by zero-carbon products with ever-increasing market competitiveness. Investment in high carbon fossil fuel industry can be risky. High carbon lock-in not only increases the difficulty of carbon neutrality, but also intensifies the risk of energy security, and it is difficult to avoid the risk of market crowding-out, resulting in huge amounts of capital waste. Consequently, decarbonization is the trend of the times, giving an edge on seeking international justice and a louder voice in the international community, and also the focus of market competitiveness. However, the target year for carbon neutrality in China is before 2060, indicating that carbon neutrality is not a short-term goal. Therefore, it is impossible and unnecessary to have it realized overnight. The opportunity of carbon neutrality should be well taken for quality growth of the economy and enhancement of people's well-being. Carbon neutrality is a long-term process which calls for thorough plans and step-by-step actions. It is also evident that along with energy revolution, carbon neutrality also brings revolutionary transformation of relations of production and development paradigm. [ABSTRACT FROM AUTHOR]

Achieving carbon neutrality requires the fundamental transformation of the development paradigm, the disruptive technologies. With efficiency-improving technologies and carbon removal technologies alone, it is possible to move further towards low carbon but hard to achieve carbon neutrality. It can only be realized through thorough decoupling from fossil energy with disruptive technologies. This revolution aiming at carbon neutrality has not only made new ground in the energy market, but also the central task which is to revolutionize zero-carbon energy production and consumption through underlying changes to the relations of production and mode of distribution, thereby pushing forward the fundamental transformation of social development paradigm. [ABSTRACT FROM AUTHOR]

China's declaration to the international community to peak CO2 emissions before 2030 and achieve carbon neutrality before 2060 is of great significance in advancing the objectives of the Paris Agreement, and has a positive and far-reaching impact on China's high-quality development. This paper expounds on responsibilities and ambitions in tackling climate change, analyzes the high-quality development opportunities brought about by CO2 emissions peak and carbon neutrality, and discusses the net zero carbon emissions transformation in the new era of ecological civilization. This paper is of the view that development towards net zero carbon emissions provides a new impetus for building a Beautiful China, and promoting ecological civilization and green development. The essence of carbon neutrality should be correctly understood so that the world will work together to improve climate resilience. China should also deepen the understanding of the principles and methodologies of climate change economics. [ABSTRACT FROM AUTHOR]

The "Proposals for Formulating the 14th Five-Year Plan (2021–2025) for National Economic and Social Development and the Long-Range Objectives Through the Year 2035" puts forth that there will be a fundamental improvement in the environment with the goal of building a Beautiful China basically. One of the key measurements of Beautiful China is carbon neutrality orientation. The task of achieving carbon neutrality is arduous, and the key difficulty of carbon neutrality lies in cities. The author believes there should be a timetable and a roadmap for carbon neutrality in cities. First, it is necessary to clarify the goal of achieving carbon emissions peak in the "14th Five-Year Plan". Second, urban renewal, old city reconstruction and new infrastructure need to be incorporated into carbon constraints, so as to strictly prevent carbon locks, and fundamentally eliminate carbon demands. Third, the new construction, expansion or reconstruction of cities needs to be oriented by carbon neutrality. [ABSTRACT FROM AUTHOR]

The eco-civilization system constitutes an important part of the system of socialism with Chinese characteristics. In order to achieve harmonious coexistence between man and nature, it is required to not only uphold and improve the eco-civilization system, but also give full play to the advantages of China's socialist system and governance system to ensure that the eco-civilization system is effectively implemented; meanwhile, it is important to apply ecological laws in a scientific manner to continuously develop and improve the system of socialism with Chinese characteristics. Ecological laws function as the scientific basis for the building of ecological systems and ecological governance. Nature-based Solutions (NbS) demand the guarantee of ecological system and improvement of ecological governance capacity. While adhering to and perfecting the eco-civilization system, it is also needed to continuously advance the modernization of ecological governance capacity. [ABSTRACT FROM AUTHOR]

The COVID-19 disease broke out globally, bringing great challenges to public health security and increasing the difficulties in constructing ecological civilization governance system. Under the leadership of the Central Committee of the Communist Party of China with Comrade Xi Jinping at its core, the Chinese Government and people have fought against the disease with courage and put people's health and safety first. Through hard work, China has made achievements in controlling the COVID-19 pandemic and accelerated the restoring of work and life back to normalcy. While continuing to control the pandemic domestically, China promotes the building of a human community with shared destiny, and plays an active role in promoting global cooperation in public health, contributing extraordinarily to global public health and world economy. Guided by Xi Jinping's Thought of Ecological Civilization, China has endeavored for modernization characterized by harmonious coexistence between man and nature. In response to the current crisis in public health and the challenges facing human–nature harmony thus incurred, the Editorial Department of Chinese Journal of Urban and Environmental Studies has co-hosted a seminar with CASS Thinktank for Eco-civilization Studies, aiming at brainstorming on and enhancing faith in continuing the building of an ecological civilization after completing the construction of a moderately well-off society in all respects. This paper intends to call for other countries to exchange and cooperate in building ecological civilization and building the world into a beautiful home for all. [ABSTRACT FROM AUTHOR]

In the context of integrating the ecological development into all aspects and the whole process of economic, political, cultural and social development, and striving to create a new era of China's socialist ecological civilization, one important aspect is that we need to construct a paradigm transformation theory for the development of ecological civilization. In establishing theories for the paradigm of ecological development, what we need most is an economic theory. However, the problem is that traditional and conventional economics, including political economics, cannot provide theoretical and methodological support for the current ecological development in China or even the world. Based on the concept, cognition and China's practice of ecological civilization, the author reflects on the economic theory and its development direction in future. [ABSTRACT FROM AUTHOR]

Emission reduction is the focus of and difficulty in addressing climate change. In choosing emission reduction targets, China needs to examine the historical trajectory of carbon emissions in developed countries and learn from their target orientations. During the evolution of the world development pattern, the status of China changed fundamentally. The goals of the 14th Five-Year Plan to address climate change should not only be pragmatic but also demonstrate moral responsibility, and should not only achieve international leadership but also achieve domestic reverse actuation. The goals of the 14th Five-Year Plan do not need to exclude reaching the peak of carbon dioxide emissions. China has advantages in the goals of the speed and scale of renewable energy development. Although the goal of net-zero carbon is impossible to achieve in the whole country, it can be tried in some regions first. On the side of demand, the target orientation of pure electric vehicle has leading value. The indicators of climate resilience, especially resilient carbon reduction and ecological carbon sequestration, etc., are also the goals of ecological civilization transformation and development. [ABSTRACT FROM AUTHOR]

The rampant spread of coronavirus disease 2019 (COVID-19) is worth examining from different angles. From the angle of urban spatial patterns and urban morphology, urban spatial agglomeration, polarization of spatial patterns, and the concept of centralization adopted in planning urban space are objective conditions that have aggravated the pandemic. This paper examines the mechanisms and effects that may have helped the spread of the pandemic. Considering the rapid spread and severe outcome of the coronavirus disease due to the spatial agglomeration of urban population, it is required to make a trade-off among economic, ecological and safe rationalities, and put safe rationality first. [ABSTRACT FROM AUTHOR]

Objective: Docetaxel has been shown to be an effective chemotherapy agent when combined with androgen deprivation therapy for hormone sensitive metastatic prostate cancer (CaP). Since very high risk CaP has a high rate of occult metastatic disease and early recurrence, we hypothesize that patients with very high risk locally advanced CaP may benefit from docetaxel-based neoadjuvant chemohormonal therapy (NCHT). Thus, we conducted a retrospective study to identify the outcome of these patients treated with NCHT followed by radical prostatectomy (RP).Patients and Methods: We retrospectively analyzed data from 177 consecutive patients who had very high risk locally advanced CaP between March 2014 and July 2017. Patients received 3 different therapies: (i) 60 men in NCHT group, (ii) 73 men in neoadjuvant hormonal therapy (NHT) group, and (iii) 44 men received immediate RP without neoadjuvant therapy (No-NT group). Surgical outcomes were analyzed and survival differences were compared by the Kaplan-Meier method.Results: The NCHT group had statistically significant higher preoperative Prostate-Specific Antigen (PSA) (P < 0.002), higher Gleason score (P < 0.002), and more advanced clinical stage (P < 0.001) than other groups. After RP, 81% (42/52) of patients in NCHT group, 73% (51/70) of patients in NHT group, and 48% (21/44) of patients in No-NT group achieved an undetectable PSA (P < 0.001). A total of 14% (6/42) patients achieving a postoperative undetectable PSA experienced biochemical recurrence in the NCHT group, with median biochemical progression-free survival (bPFS) time of 19 months; 47% (24/51) experienced biochemical recurrence in the NHT group, with median bPFS time of 13 months; 81% (17/21) experienced biochemical recurrence in the No-NT group, with median bPFS time of 9 months (P < 0.001). The median follow-up time of 3 groups was 12.5 months in the NCHT group, 18.3 months in the NHT group, and 22.8 months in the No-NT group (P = 0.01).Conclusion: Despite having poorer prognostic factors, the NCHT group had better bPFS time after surgery compared to NHT and No-NT groups. Randomized controlled investigations are needed to validate these results and further follow-up is required for survival endpoints. [ABSTRACT FROM AUTHOR]

China's ecological environment construction has undergone three phases, i.e. the agriculture-based development phase with low productivity not long after the founding of the People's Republic of China (P.R.C.), the industrial development phase after the adoption of reform and opening-up policy, and the phase toward ecological civilization, each of which has its own features, challenges, responsive measures and achievements. From the year 1949 to the adoption of reform and opening up policy, the Chinese society was characterized by farming culture on the whole, facing problems such as frequent natural disasters, shortage in food production and low urbanization level. To jump out of the Malthusian Trap, the founders of the P.R.C. led people to prevent floods by water control, water conservancy projects and reclamation of wasteland, which alleviated but did not solve the problems because China still suffered poverty and backwardness, and failed to shake off the Malthusian Curse. After the adoption of the reform and opening-up policy, the rapid progress in industrialization and urbanization has liberated farmers from land and greatly improved labor productivity; meanwhile, some lands were released from farmers' hand, which not only made the value of land resources much higher but also enabled land rehabilitation and ecological self-restoration. Although rapid industrialization and urbanization enormously boosted productive forces and accumulated immense amount of material wealth, but since the beginning of the 21st century, China's development has been drawn near to the ecological red line, environmental threshold and resources upper limit of industrial development, constantly challenged by sustainable development. After 2010, China has initiated the transformation to ecological civilization, featuring ecological protection, pollution control and resource conservation, aiming to promote the harmonious development between man and nature. [ABSTRACT FROM AUTHOR]

China's reform and opening up is an all-round transformation and development. The harmonious coexistence of man and nature is the foundation and starting point of social and economic development, and the future direction of human society. Reform and opening up does not come from nowhere, and green development is a product and need of historical development. Before the reform and opening up, the conflict between man and nature caused ecological imbalance induced by the destruction of nature that aimed to meet basic food needs under the conditions of low productivity in a traditional agricultural society. The 40 years of reform and opening up have seen the initial completion of industrialization and urbanization in compressed time. During this process, the conflict between man and nature has evolved into expensive material consumption and ever-expanding desire for non-material enjoyments, leading to the pollution crisis endangering humans' living environment and natural sustainability. On the 40th anniversary of reform and opening-up policy, it is necessary to understand this evolution process. By summarizing the achievements and discerning the problems of green transformation, this paper analyzes the direct and internal impetus, explores the theoretical basis and shares the outlook on future development. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the incidence and the clinicopathological features of incidental prostate cancer detected in radical cystoprostatectomy (RCP) specimens in Chinese men and to estimate the oncological risk of prostate apex-sparing surgery for such patients. Methods: The clinical data and pathological feature of 504 patients who underwent RCP for bladder cancer from January 1999 to March 2013 were retrospectively reviewed. Whole mount serial section of the RCP specimens were cut transversely at 3–4 mm intervals and examined in same pathological institution. Results: Thirty-four out of 504 patients (6.8%) had incidental prostate cancer with a mean age of 70.3 years. 12 cases (35.2%) were diagnosed as significant disease. 4 cases were found to have apex involvement of adenocarcinoma of the prostate while in 5 cases the prostate stroma invasion by urothelial carcinoma were identified (one involved prostate apex). The mean follow-up time was 46.4±33.8 months. Biochemical recurrence occurred in 3 patients but no prostate cancer-related death during the follow-up. There was no statistical significance in cancer specific survival between the clinically significant and insignificant cancer group. Conclusions: The prevalence of incidental prostate cancer in RCP specimens in Chinese patients was remarkably lower than in western people. Most of the incidental prostate cancer was clinically insignificant and patient's prognosis was mainly related to the bladder cancer. Sparing the prostate apex was potentially associated with a 1.0% risk of leaving significant cancer of the prostate or urothelial carcinoma. [ABSTRACT FROM AUTHOR]

The aim of the study was to compare the clinical outcome and the cost-effectiveness between retrograde intra renal surgery (RIRS) and mini-percutaneous nephrolithotripsy (mPCNL) for the management of single renal stone of 2-3 cm in Chinese medical setting. From May 2005 to February 2011, 115 patients with solitary renal calculi were treated either by RIRS or mPCNL. 56 patients were in RIRS group while 59 were in mPCNL group. Patients' demographics between the two groups, in terms of gender, age, BMI, history of ESWL as well as stone side, stone location and stone size were comparable. Peri-operative course, clinical outcome, complication rates and medical cost were compared. The effective quotient (EQ) of two groups was calculated. Data were analyzed using Fisher's exact test, Chi-square test and Student's t test. EQ for RIRS and mPCNL were 0.52 and 0.90. The initial stone-free rate (SFR) of RIRS group and mPCNL group was 71.4 and 96.6 %, respectively ( P = 0.000). The mean procedure number was 1.18 in RIRS group and 1.03 in mPCNL group, respectively ( P = 0.035). The operative time for RIRS was longer ( P = 0.000) while the mean hospital stay was shorter ( P = 0.000). There was no statistical difference in peri-operative complications between the groups. The initial hospitalization cost, laboratory and radiology test cost of RIRS group were lower ( P = 0.000). However, counting the retreatment cost in the two groups, the total medical expenditure including the overall hospitalization cost, overall laboratory and radiology test cost and post-operative out-patient department (OPD) visit cost was similar between two groups. In conclusion, with similar total medical cost, mPCNL achieved faster stone clearance and lower retreatment rate without major complications, which implied higher cost-effectiveness for the treatment of single renal stone of 2-3 cm in Chinese medical setting. RIRS is also a safe and reliable choice for patients having contraindications or preference against mPCNL. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the antifibrotic role of captopril during ureteral scarring in a New Zealand rabbit model. Materials and Methods: The tissue expression and the fluctuation of EGF, TGF-β, FN, Col Ia1, Col Ia2 and Col III of the impaired ureter and the contralateral normal ureter were investigated by RT-PCR. The histological changes of the specimens were studied. When the sensitive markers had been selected, 10 New Zealand rabbits were randomly assigned to a captopril group and a control group. The specimens were harvested 2 weeks after the injury and then the histological examination and RT-PCR were performed. Results: By RT-PCR screening, EGF, TGF-β, FN, Col Ia1 and Col Ia2 were found to be significantly related to ureteral scarring (p < 0.05) confirmed by histological examination. The peak level of EGF, TGF-β and Col Ia1 appeared at 2 weeks after the injury, while for Fn and Col Ia2 it was at 3 and 4 weeks after the injury. An obvious reduction of fibrotic scarring was observed in the captopril group. The expression of EGF, Fn and Col Ia2 in the captopril group was significantly lower than in the control group (p < 0.05) after the treatment. Conclusions: EGF, TGF-β, Col Ia1, Col Ia2 and FN seemed to have an important role in the ureteral scarring after injury. Captopril might partially inhibit the fibrotic process by blocking the EGF, Col Ia2 and FN pathway so that it could be a promising treatment after ureteral injury. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The transition from an oil-dependent century to a carbon-neutral era dominated by renewable energy will reshape the pattern of global energy security. Based on the characteristics of uneven, heterogeneous, and scattered distribution of fossil fuels, this study indicates that the traditional energy security dominated by fossil fuels is in a geographical dilemma, while renewable energy, with its natural advantages, provides a new opportunity to break the shackles of this dilemma on China' s energy security. Moreover, this study empirically tested the relationship between the usage of renewable energy and geopolitical patterns of energy risks using time series data from 1990 to 2020. The results showed that the usage of renewable energy represented by wind energy, solar energy, hydro energy, biomass energy, etc., significantly reduced the geopolitical risks generated by China' s long-term dependence on fossil fuel imports and provided a guarantee for China' s national energy security. The results were confirmed by the robust tests. It is hoped that this study can enrich the existing literature on national energy security and provide a theoretical basis for the strategic layout of national energy securi -ty in the context of carbon neutrality. Additionally, the research has policy implications for strengthening China' s strategic leadership in the world energy pattern and is conducive to the realization of national rejuvenation and the construction of a modern energy power. [ABSTRACT FROM AUTHOR]

In this article, it is proposed that mitigation options by developing countries will be assessed against their impacts on human development goals. Human development goals take priority mitigation but low emission alternatives can be identified without compromising those goals. Three types of mitigation actions can be taken: voluntary, conditional and obligatory. Voluntary actions aim at no-regret emission reductions, based on autonomous energy efficiency improvement during the course of economic growth. Additional emission cuts, mainly in developing countries, will be conditional to transfer of technologies and financial assistance from developed countries. The obligatory part is morally based, discouraging luxurious and wasteful emissions. These options highlight the need for development, while at the same time focus on emissions reductions. First, developing countries will be able to pursue human development goals and welcome climate policies that contribute to such goals. Second, assistance from developed countries will enable them to make additional emission reductions. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second most common cancer in males worldwide. The Gleason scoring system, which classifies the pathological growth pattern of cancer, is considered one of the most important prognostic factors for PCa. Compared to indolent PCa, PCa with high Gleason score (h‐GS PCa, GS ≥ 8) has greater clinical significance due to its high aggressiveness and poor prognosis. It is crucial to establish a rapid, non‐invasive diagnostic modality to decipher patients with h‐GS PCa as early as possible. In this study, ferric nanoparticle‐assisted laser desorption/ionization mass spectrometry (FeNPALDI‐MS) to extract prostate fluid metabolic fingerprint (PSF‐MF) is employed and combined with the clinical features of patients, such as prostate‐specific antigen (PSA), to establish a multi‐modal diagnosis assisted by machine learning. This approach yields an impressive area under the curve (AUC) of 0.87 to diagnose patients with h‐GS, surpassing the results of single‐modal diagnosis using only PSF‐MF or PSA, respectively. Additionally, using various screening methods, six key metabolites that exhibit greater diagnostic efficacy (AUC = 0.96) are identified. These findings also provide insights into related metabolic pathways, which may provide valuable information for further elucidation of the pathological mechanisms underlying h‐GS PCa. [ABSTRACT FROM AUTHOR]

In the present study, we hypothesized that buckwheat honey (BH) should be regarded as a potential alternative to antibacterial and antioxidant agent in liquid storage of boar semen. To this end, boar semen was firstly studied for in vitro dose tolerability to BH by measuring sperm progressive motility. The optimum progressive motility of boar spermatozoa was observed in extender with 0.5% and 0.6% BH addition. Afterward, sperm quality parameters, bacterial profile and composition, total antioxidant (T-AOC), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels of control, BH supplementation, antibiotics supplementation, and incorporated supplementation were compared during liquid storage period, to further investigate antibacterial and antioxidant properties of BH. The results showed that BH supplementation significantly improved sperm motility, acrosome integrity, plasma membrane integrity, inhibited opportunistic bacterial growth, and altered microbial compositions at the end of preservation. Additionally, T-AOC, SOD, and CAT levels were significantly higher in the BH supplementation group than those in the control and antibiotic supplementation group, whereas MDA level exhibited opposite change pattern. Importantly, BH addition to the extender was able to exert a synergistic effect in combination of antibiotic use. Our findings suggested that the appropriate concentrations (0.5% and 0.6%) of BH were added to the extender could act antibacterial and antioxidant roles in liquid preservation of boar semen. [ABSTRACT FROM AUTHOR]

Objectives. To identify risk factors associated with the prognosis of pertussis-like coughing. Methods. A retrospective study on children hospitalized with pertussis-like coughing from 2018 to 2019. We collected all the case data from medical records including age, gender, vaccination, clinical symptoms, complication, pathogens, white blood cell (WBC) count, lymphocyte ratio, application of macrolide antibiotics, usage of sulfamethoxazole, and usage of inhaled glucocorticoids. Logistic regression was used in this study. Results. A total of 213 hospitalized children with pertussis-like coughing were included in this study. About 70 children were cured within 2 weeks. One120 children were cured from 2 weeks to 3 months, including cases of initial attack and relapse. Symptoms lasting longer than 3 months accounts for 10.8%. Bordetella pertussis, WBC count >20 × 109/L and lymphocyte ratio >60% were associated with poor prognosis (P <.05). Conclusions. Bordetella pertussis, WBC count, and lymphocyte ratio are independent risk factors for poor prognosis. [ABSTRACT FROM AUTHOR]

Background: The mammalian intestinal tract harbors diverse and dynamic microbial communities that play pivotal roles in host health, metabolism, immunity, and development. Average daily gain (ADG) is an important growth trait in meat rabbit industry. The effects of gut microbiota on ADG in meat rabbits are still unknown. Results: In this study, we investigated the dynamic distribution of gut microbiota in commercial Ira rabbits from weaning to finishing and uncover the relationship between the microbiota and average daily gain (ADG) via 16S rRNA gene sequencing. The results indicated that the richness and diversity of gut microbiota significantly increased with age. Gut microbial structure was less variable among finishing rabbits than among weaning rabbits. The relative abundances of the dominant phyla Firmicutes, Bacteroidetes, Verrucomicrobia and Cyanobacteria, and the 15 predominant genera significantly varied with age. Metagenomic prediction analysis showed that both KOs and KEGG pathways related to the metabolism of monosaccharides and vitamins were enriched in the weaning rabbits, while those related to the metabolism of amino acids and polysaccharides were more abundant in the finishing rabbits. We identified 34 OTUs, 125 KOs, and 25 KEGG pathways that were significantly associated with ADG. OTUs annotation suggested that butyrate producing bacteria belong to the family Ruminococcaceae and Bacteroidales_S24-7_group were positively associated with ADG. Conversely, Eubacterium_coprostanoligenes_group, Christensenellaceae_R-7_group, and opportunistic pathogens were negatively associated with ADG. Both KOs and KEGG pathways correlated with the metabolism of vitamins, basic amino acids, and short chain fatty acids (SCFAs) showed positive correlations with ADG, while those correlated with aromatic amino acids metabolism and immune response exhibited negative correlations with ADG. In addition, our results suggested that 10.42% of the variation in weaning weight could be explained by the gut microbiome. Conclusions: Our findings give a glimpse into the dynamic shifts in gut microbiota of meat rabbits and provide a theoretical basis for gut microbiota modulation to improve ADG in the meat rabbit industry. [ABSTRACT FROM AUTHOR]

High‐throughput metabolic fingerprinting has been deemed one of the most promising strategies for addressing the high false positive rate of prostate cancer (PCa) diagnosis in the prostate‐specific antigen (PSA) gray zone. However, the current metabolic fingerprinting remains challenging in achieving high‐precision metabolite detection in complex biological samples (e.g., serum and urine). Herein, a novel self‐assembly MoS2/MXene heterostructure nanocomposite with a tailored doping ratio of 10% is presented as a matrix for laser desorption ionization mass spectrometry analysis in clinical biosamples. Notably, owing to the two‐dimensional architecture and doping effect, MoS2/MXene demonstrates favorable laser desorption ionization performance with low adsorption energy, which is evidenced by efficient urinary metabolic fingerprinting with an enhanced area under curve (AUC) diagnosis capability of 0.959 relative to that of serum metabolic fingerprinting (AUC = 0.902) for the diagnosis of PCa in the PSA gray zone. Thus, this MoS2/MXene heterostructure is anticipated to offer a novel strategy to precisely and noninvasively diagnose PCa in the PSA gray zone. [ABSTRACT FROM AUTHOR]

We reported genomic profiling, clinical characterization, and treatment efficacy of available therapeutic agents in the largest multicenter cohort of patients with FH-deficient renal cell carcinoma (RCC) to date. First-line combination therapy with an immune checkpoint inhibitor plus a tyrosine kinase inhibitor (ICI/TKI) was associated with more favorable outcomes in comparison to other first-line therapies, including bevacizumab plus erlotinib and TKI monotherapy, suggesting ICI/TKI combinations could be promising in advanced FH-deficient RCC. Further randomized studies in larger data sets are needed for independent validation of these findings. FH-deficient renal cell carcinoma (RCC) is a rare and exceptionally aggressive RCC subtype. There is currently limited understanding of the molecular alterations, pathogenesis, survival outcomes, and systemic therapy efficacy for this cancer. To perform a retrospective multicenter analysis of molecular profiling and clinical outcomes for patients with FH-deficient RCC, with an emphasis on treatment response to first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI/TKI) versus bevacizumab plus erlotinib (Bev/Erlo) combination therapy in patients with advanced disease. The study included 77 cases of FH-deficient RCC from 15 centers across China. Clinical characteristics, molecular correlates, 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging, and treatment outcomes were analyzed. A total of 77 patients were identified, including 70 cases with a germline FH alteration (hereditary leiomyomatosis RCC syndrome [HLRCC]-associated RCC) and seven patients with somatic FH loss. Recurrent pathogenic alterations were found in NF2 (six/57, 11%), CDH1 (six/57, 11%), PIK3CA (six/57, 11%), and TP53 (five/57, 8.8%). Sixty-seven patients were evaluable for response to first-line systemic therapy with Bev/Erlo (n = 12), TKI monotherapy (n = 29), or ICI/TKI (n = 26). ICI/TKI combination therapy was associated with more favorable overall survival on systemic treatment (hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.04–0.90) and progression-free survival on first-line therapy (HR 0.22, 95% CI 0.07–0.71) compared to Bev/Erlo combination therapy. The main limitation is the retrospective study design. We described the genomic characteristics of FH-deficient RCC in an Asian population and observed a favorable response to ICI/TKI combinational therapy among patients with advanced disease. This real-world study provides evidence supporting the antitumour activity of combining molecular targeted therapy plus immunotherapy for kidney cancer deficient in fumarate hydratase. Further studies are needed to investigate the efficacy of this combination strategy in this rare cancer. [ABSTRACT FROM AUTHOR]

To explore the diagnostic value of the Prostate Imaging–Reporting and Data System version 2.1 (PI-RADS v2.1) for clinically significant prostate cancer (CSPCa) in patients with a history of transurethral resection of the prostate (TURP), we conducted a retrospective study of 102 patients who underwent systematic prostate biopsies with TURP history. ROC analyses and logistic regression analyses were performed to demonstrate the diagnostic value of PI-RADS v2.1 and other clinical characteristics, including PSA and free/total PSA (F/T PSA). Of 102 patients, 43 were diagnosed with CSPCa. In ROC analysis, PSA, F/T PSA, and PI-RADS v2.1 demonstrated significant diagnostic value in detecting CSPCa in our cohort (AUC 0.710 (95%CI 0.608–0.812), AUC 0.768 (95%CI 0.676–0.860), AUC 0.777 (95%CI 0.688–0.867), respectively). Further, PI-RADS v2.1 scores of the peripheral and transitional zones were analyzed separately. In ROC analysis, PI-RADS v2.1 remained valuable in identifying peripheral-zone CSPCa (AUC 0.780 (95%CI 0.665–0.854; p < 0.001)) while having limited capability in distinguishing transitional zone lesions (AUC 0.533 (95%CI 0.410–0.557; p = 0.594)). PSA and F/T PSA retain significant diagnostic value for CSPCa in patients with TURP history. PI-RADS v2.1 is reliable for detecting peripheral-zone CSPCa but has limited diagnostic value when assessing transitional zone lesions. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second leading cause of cancer-related deaths of men. Bmi-1, a member of PcG family of proteins, has been implicated in the pathogenesis of prostate cancer, and disturbed profile of microRNAs (miRNAs) has been found in prostate cancer tissues. How Bmi-1 is regulated by miRNAs is unclear. In this study, we screened 18 miRNAs that potentially repress the expression of Bmi-1 using a dual luciferase system and found that 12 miRNAs could bind with the 3′-untranslated region of Bmi-1 mRNA. Using qRT-PCR, we found that expression of miR-221, -15a, and -30d was significantly reduced in prostate cancer tissues. Subsequent functional study indicated that miR-221 and miR-30d can repress prostate cancer cell proliferation, and this effect can be partially rescued by Bmi-1 overexpression. Our study constructs the relation between downregulated miR-221 and miR-30d and prostate cancer pathogenesis. These results indicate that miR-221 and miR-30d are candidate tumor suppressor miRNAs in prostate cancer and therefore serve as potential clinical classification markers and therapeutic targets for human prostate cancer. [ABSTRACT FROM AUTHOR]

Surface-enhanced Raman spectroscopy (SERS) has gained increasing importance in molecular detection due to its high specificity and sensitivity. Complex biofluids (e.g., cell lysates and serums) typically contain large numbers of different bio-molecules with various concentrations, making it extremely challenging to be reliably and comprehensively characterized via conventional single SERS spectra due to uncontrollable electromagnetic hot spots and irregular molecular motions. The traditional approach of directly reading out the single SERS spectra or calculating the average of multiple spectra is less likely to take advantage of the full information of complex biofluid systems. Herein, we propose to construct a spectral set with unordered multiple SERS spectra as a novel representation strategy to characterize full molecular information of complex biofluids. This new SERS representation not only contains details from each single spectra but captures the temporal/spatial distribution characteristics. To address the ordering-independent property of traditional chemometric methods (e.g., the Euclidean distance and the Pearson correlation coefficient), we introduce Wasserstein distance (WD) to quantitatively and comprehensively assess the quality of spectral sets on biofluids. WD performs its superiority for the quantitative assessment of the spectral sets. Additionally, WD benefits from its independence of the ordering of spectra in a spectral set, which is undesirable for traditional chemometric methods. With experiments on cell lysates and human serums, we successfully achieve the verification for the reproducibility between parallel samples, the uniformity at different positions in the same sample, the repeatability from multiple tests at one location of the same sample, and the cardinality effect of the spectral set. SERS spectral sets also manage to distinguish different classes of human serums and achieve higher accuracy than the traditional prostate-specific antigen in prostate cancer classification. The proposed SERS spectral set is a robust representation approach in accessing full information of biological samples compared to relying on a single or averaged spectra in terms of reproducibility, uniformity, repeatability, and cardinality effect. The application of WD further demonstrates the effectiveness and robustness of spectral sets in characterizing complex biofluid samples, which extends and consolidates the role of SERS. [Display omitted] • A novel SERS representation strategy for dynamic biofluids. • Statistical analysis for unordered spectral data. • Reliability, consistency, and reproducibility of the strategy. • Spectral details and distribution characteristics were captured. [ABSTRACT FROM AUTHOR]

Background: T cell stress response state (TSTR), as a novel immune concept previous studies have proposed, has not yet been explored in prostate cancer (PC). As a type of cellular efflux, exosomes play important roles in the occurrence and development of PC.Here, we conducted a combined analysis on extracellular vesicle related genes (EVRGs) in PC using data from single-cell RNA (scRNA), spatial transcriptome (ST), and bulk RNA sequencing.Preliminary findings have revealed that heat shock protein family H (Hsp110) member 1 (HSPH1) possesses two identities, one being EVRGs and the other being a member of the heat shock protein family involved in TSTR, which may promote the differentiation of conventional T cells towards Th1 or Th2 cells through the pathway of IL2-MYC-IL2RA, thereby promoting the increase of CD8 + T cells in the tumor area, especially in the invasive zone, and inhibiting the invasion of PCs. We also notice the negative response of HSPH1 + CD8 + T cell related genes in immune checkpoint blockade (ICB). Western blot (WB) and droplet digital Polymerase Chain Reaction (ddPCR) demonstrated that the mRNA and protein levels of HSPH1 in EVs of PCs were significantly higher than those in adjacent tissues.Results above indicate the potential of HSPH1 as a critical therapeutic target in PC.Method: T cell stress response state (TSTR), as a novel immune concept previous studies have proposed, has not yet been explored in prostate cancer (PC). As a type of cellular efflux, exosomes play important roles in the occurrence and development of PC.Here, we conducted a combined analysis on extracellular vesicle related genes (EVRGs) in PC using data from single-cell RNA (scRNA), spatial transcriptome (ST), and bulk RNA sequencing.Preliminary findings have revealed that heat shock protein family H (Hsp110) member 1 (HSPH1) possesses two identities, one being EVRGs and the other being a member of the heat shock protein family involved in TSTR, which may promote the differentiation of conventional T cells towards Th1 or Th2 cells through the pathway of IL2-MYC-IL2RA, thereby promoting the increase of CD8 + T cells in the tumor area, especially in the invasive zone, and inhibiting the invasion of PCs. We also notice the negative response of HSPH1 + CD8 + T cell related genes in immune checkpoint blockade (ICB). Western blot (WB) and droplet digital Polymerase Chain Reaction (ddPCR) demonstrated that the mRNA and protein levels of HSPH1 in EVs of PCs were significantly higher than those in adjacent tissues.Results above indicate the potential of HSPH1 as a critical therapeutic target in PC.Result: T cell stress response state (TSTR), as a novel immune concept previous studies have proposed, has not yet been explored in prostate cancer (PC). As a type of cellular efflux, exosomes play important roles in the occurrence and development of PC.Here, we conducted a combined analysis on extracellular vesicle related genes (EVRGs) in PC using data from single-cell RNA (scRNA), spatial transcriptome (ST), and bulk RNA sequencing.Preliminary findings have revealed that heat shock protein family H (Hsp110) member 1 (HSPH1) possesses two identities, one being EVRGs and the other being a member of the heat shock protein family involved in TSTR, which may promote the differentiation of conventional T cells towards Th1 or Th2 cells through the pathway of IL2-MYC-IL2RA, thereby promoting the increase of CD8 + T cells in the tumor area, especially in the invasive zone, and inhibiting the invasion of PCs. We also notice the negative response of HSPH1 + CD8 + T cell related genes in immune checkpoint blockade (ICB). Western blot (WB) and droplet digital Polymerase Chain Reaction (ddPCR) demonstrated that the mRNA and protein levels of HSPH1 in EVs of PCs were significantly higher than those in adjacent tissues.Results above indicate the potential of HSPH1 as a critical therapeutic target in PC.Conclusion: T cell stress response state (TSTR), as a novel immune concept previous studies have proposed, has not yet been explored in prostate cancer (PC). As a type of cellular efflux, exosomes play important roles in the occurrence and development of PC.Here, we conducted a combined analysis on extracellular vesicle related genes (EVRGs) in PC using data from single-cell RNA (scRNA), spatial transcriptome (ST), and bulk RNA sequencing.Preliminary findings have revealed that heat shock protein family H (Hsp110) member 1 (HSPH1) possesses two identities, one being EVRGs and the other being a member of the heat shock protein family involved in TSTR, which may promote the differentiation of conventional T cells towards Th1 or Th2 cells through the pathway of IL2-MYC-IL2RA, thereby promoting the increase of CD8 + T cells in the tumor area, especially in the invasive zone, and inhibiting the invasion of PCs. We also notice the negative response of HSPH1 + CD8 + T cell related genes in immune checkpoint blockade (ICB). Western blot (WB) and droplet digital Polymerase Chain Reaction (ddPCR) demonstrated that the mRNA and protein levels of HSPH1 in EVs of PCs were significantly higher than those in adjacent tissues.Results above indicate the potential of HSPH1 as a critical therapeutic target in PC. [ABSTRACT FROM AUTHOR]

(C) Kaplan-Meier curves for time to castration resistance in patients with germline BRCA2 alteration and germline BRCA2 wild-type gl Additionally, concurrent I HSD3B1 i genotype was detected in 348 (71.0%) of the 490 studied patients. (B) Kaplan-Meier curves for time to castration resistance in patients with germline DDR alteration and germline DDR wild-type. Germline deleterious alterations interrupting the function of DNA damage repair (DDR) have proven to be related to a high risk of prostate cancer (PCa), which are recommended for testing in general practice.1 Moreover, the genetic background has recently emerged as a potential factor in racial diversity, especially in the epidemiology of PCa.2 Since our understanding of the genomics was mostly derived from the Caucasian population, we conducted a real-world multicenter retrospective study of 490 patients with PCa across distinct clinical states in order to better elucidate the prevalence and clinical implication of rare germline deleterious alterations in Chinese men. [Extracted from the article]

Abstract: Background: The purpose of this study was to comparatively evaluate the efficacy of pyrosequencing (PS) and Sanger sequencing (SS) methods for detecting K-Ras codon 12 and 13 mutations in formalin-fixed paraffin-embedded (FFPE) prostate cancer (PCa) samples from Chinese patients. Methods: The cancer cell lines, including the LS174T G12D mutant (GGT to GAT) and the COLO320 wild-type, were tested to determine the limitation of detection and reproducibility of the PS method. In addition, 101 PCa patient samples, 13 benign prostatic hyperplasia (BPH) and 12 normal adjacent tissue samples, were assayed by PS and SS to evaluate their detection abilities for K-Ras mutations in codons 12 and 13. Results: The PS assay was able to reproducibly detect 5% mutant alleles and had an intra-assay variability of 4.21% and inter-assay variability of 11.37%. The PS assay detected a higher number of K-Ras mutations in PCa samples than the SS assay (8.91% vs. 3.96%). Correlation and stratification analyses of the PCa samples and K-Ras mutation status revealed no associations between age, serum prostate specific antigen (PSA), depth of invasion (pT category), or Gleason score. Conclusions: We demonstrated that the PS method detected more K-Ras mutations in codons 12 and 13 of FFPE prostate cancer samples from Chinese patients than the traditional SS method. In addition, the K-Ras mutation was more frequent in Chinese population than in Western populations but was similar to that of other Eastern populations, suggesting that these K-Ras mutations may contribute to the pathogenesis of prostate carcinoma in Asian patients. [Copyright &y& Elsevier]

The focus of this article was employment creation by developing forest park tourism industries in China. Analysis of the statistical data and an input-output approach showed that 1 direct job opportunity in tourism industries created 1.15 other job opportunities. In the high, middle, and low scenarios, the total predicted employment in forest park tourism was 8.14, 5.13, and 4.82 million, respectively, from 2011 to 2020. These results demonstrate the importance of considering employment within forest park tourism as a viable option. [ABSTRACT FROM AUTHOR]

Background: Tumor‐infiltrating immune cells participate in the initiation and progression of prostate adenocarcinoma (PRAD). However, it is not fully known how immune infiltration affects the development of PRAD and its clinical presentation. Methods: Herein, we investigated the immune infiltration phenotypes in PRAD based on transcriptome profiles, methylation profiles, somatic mutation, and copy number variations. We also developed an immune prognostic model (IPM) to identify unfavorable prognosis. To verify this model, immunohistochemistry staining was performed on a cohort of PRAD samples. Moreover, we constructed a nomogram to assess the survival of PRAD incorporating immune infiltration and other clinical features. Results: We categorized PRAD patients into high and low‐level clusters based on immune infiltration phenotypes. The patients in the high‐level clusters had worse survival than their low‐level counterparts. Gene set enrichment analysis indicated that both anti‐ and pro‐tumor terms were enriched in high‐level cluster. Moreover, we identified a positive correlation between anti‐ and pro‐tumor immune cells in PRAD microenvironment. Notably, Somatic mutation analysis showed patients in high‐level cluster had a higher somatic mutation burden of KMT2D, HSPA8, CHD7, and MAP1A. In addition, we developed an IPM with robust predictive ability. The model can distinguish high‐risk PRAD patients with poor prognosis from low‐risk PRAD patients in both training and another three independent validation datasets. Besides, we constructed a nomogram incorporating Gleason score, pathological T stage, and IPM for the prognosis prediction of PRAD patients, which displayed robust predictive ability and might contribute to clinical practice. Conclusion: Our work illustrated the immune infiltration phenotypes strongly related to the poor prognosis of PRAD patients, and highlighted the potential of the IPM to identify unfavorable tumor features. [ABSTRACT FROM AUTHOR]

Docetaxel-based chemotherapy, as the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC), has succeeded in helping quite a number of patients to improve quality of life and prolong survival time. However, almost half of mCRPC patients are not sensitive to docetaxel chemotherapy initially. This study aimed to establish models to predict sensitivity to docetaxel chemotherapy in patients with mCRPC by using serum surface-enhanced Raman spectroscopy (SERS). A total of 32 mCPRC patients who underwent docetaxel chemotherapy at our center from July 2016 to March 2018 were included in this study. Patients were dichotomized in prostate-specific antigen (PSA) response group (n = 1 7) versus PSA failure group (n = 1 5) according to the response to docetaxel. In total 64 matched spectra from 32 mCRPC patients were obtained by using SERS of serum at baseline (q 0) and after 1 cycle of docetaxel chemotherapy (q 1). Comparing Raman peaks of serum samples at baseline (q 0) between two groups, significant differences revealed at the peaks of 638, 810, 890 (p < 0. 0 5) and 1136 cm − 1 (p < 0. 0 1). The prediction models of peak 1363 cm − 1 and principal component analysis and linear discriminant analysis (PCA–LDA) based on Raman data were established, respectively. The sensitivity and specificity of the prediction models were 71%, 80% and 69%, 78% through the way of leave-one-out cross-validation. According to the results of five-cross-validation, the PCA–LDA model revealed an accuracy of 0.73 and AUC of 0.83. [ABSTRACT FROM AUTHOR]

Neuroendocrine prostate cancer is one of the most aggressive subtypes of prostate tumor. Although much progress has been made in understanding the development of neuroendocrine prostate cancer, the cellular architecture associated with neuroendocrine differentiation in human prostate cancer remain incompletely understood. Here, we use single-cell RNA sequencing to profile the transcriptomes of 21,292 cells from needle biopsies of 6 castration-resistant prostate cancers. Our analyses reveal that all neuroendocrine tumor cells display a luminal-like epithelial phenotype. In particular, lineage trajectory analysis suggests that focal neuroendocrine differentiation exclusively originate from luminal-like malignant cells rather than basal compartment. Further tissue microarray analysis validates the generality of the luminal phenotype of neuroendocrine cells. Moreover, we uncover neuroendocrine differentiation-associated gene signatures that may help us to further explore other intrinsic molecular mechanisms deriving neuroendocrine prostate cancer. In summary, our single-cell study provides direct evidence into the cellular states underlying neuroendocrine transdifferentiation in human prostate cancer. Using single-cell RNA sequencing, Dong, Miao, Wang et al. profile the transcriptomes of 21,292 cells from biopsies of 6 castration-resistant prostate cancers. They find that all neuroendocrine tumor cells display a luminal-like epithelial phenotype, providing insights into the cellular states underlying neuroendocrine transdifferentiation in human prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: Reprogramming of cellular metabolism is profoundly implicated in tumorigenesis and can be exploited to cancer treatment. Cancer cells are known for their propensity to use glucose‐dependent glycolytic pathway instead of mitochondrial oxidative phosphorylation for energy generation even in the presence of oxygen, a phenomenon known as Warburg effect. The type II beta regulatory subunit of protein kinase A (PKA), PRKAR2B, is highly expressed in castration‐resistant prostate cancer (CRPC) and contributes to tumour growth and metastasis. However, whether PRKAR2B regulates glucose metabolism in prostate cancer remains largely unknown. Materials and methods: Loss‐of‐function and gain‐of‐function studies were used to investigate the regulatory role of PRKAR2B in aerobic glycolysis. Real‐time qPCR, Western blotting, luciferase reporter assay and chromatin immunoprecipitation were employed to determine the underlying mechanisms. Results: PRKAR2B was sufficient to enhance the Warburg effect as demonstrated by glucose consumption, lactate production and extracellular acidification rate. Mechanistically, loss‐of‐function and gain‐of‐function studies showed that PRKAR2B was critically involved in the tumour growth of prostate cancer. PRKAR2B was able to increase the expression level of hypoxia‐inducible factor 1α (HIF‐1α), which is a key mediator of the Warburg effect. Moreover, we uncovered that HIF‐1α is a key transcription factor responsible for inducing PRKAR2B expression in prostate cancer. Importantly, inhibition of glycolysis by the glycolytic inhibitor 2‐deoxy‐d‐glucose (2‐DG) or replacement of glucose in the culture medium with galactose (which has a much lower rate than glucose entry into glycolysis) largely compromised PRKAR2B‐mediated tumour‐promoting effect. Similar phenomenon was noticed by genetic silencing of HIF‐1α. Conclusions: Our study identified that PRKAR2B‐HIF‐1α loop enhances the Warburg effect to enable growth advantage in prostate cancer. [ABSTRACT FROM AUTHOR]

Castration‐resistant prostate cancer (CRPC) causes most of the deaths in patients with prostate cancer (PCa). The androgen receptor (AR) axis plays an important role in castration resistance. Emerging studies showed that the lysine demethylase KDM4B is a key molecule in AR signaling and turnover, and autophagy plays an important role in CRPC. However, little is known about whether KDM4B promotes CRPC progression by regulating autophagy. Here we used an androgen‐independent LNCaP (LNCaP‐AI) cell line to assay aberrant KDM4B expression using qPCR and western blot analysis and investigated the function of KDM4B in regulating cell proliferation. We found that KDM4B was markedly increased in LNCaP‐AI cells compared with LNCaP cells. KDM4B level was significantly correlated with the Gleason score in PCa tissues. In vitro, KDM4B overexpression in CRPC cells promoted cell proliferation, whereas knockdown of KDM4B significantly inhibited cell proliferation. Upregulated KDM4B contributed to activate Wnt/β‐catenin signaling and autophagy. Moreover, KDM4B activated autophagy by regulating the Wnt/β‐catenin signaling. Finally, we demonstrated that autophagy inhibition attenuated KDM4B‐induced CRPC cell proliferation. Our results provided novel insights into the function of KDM4B‐driven CRPC development and indicated that KDM4B may be served as a potential target for CRPC therapy. [ABSTRACT FROM AUTHOR]

Objective: To assess the use of the cell cycle progression (CCP) score versus actual risk stratification practice in making treatment decisions for prostate cancer patients with locally adverse pathology after radical prostatectomy (RP). Patients and methods: Men with adverse pathologic features, pT3 or positive surgical margins who underwent RP in 2010–2014 at Renji hospital were retrospectively analyzed. The primary outcome was biochemical recurrence (BCR) after RP. RNA was quantified from paraffin-embedded RP specimens. The CCP score was calculated as average expression of 31 CCP genes, normalized to 15 housekeeper genes. The prognostic utility of the CCP score was assessed using Kaplan–Meier analysis and multivariable Cox proportional hazards model. Results: Among the 100 men identified, 5-year BCR-free survival for the low- (< 0), intermediate- (0–1) and high- (> 1) CCP score groups was 89.3%, 38.8%, and 12.9%, respectively. In multivariable models adjusting for clinical and pathological variables with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score, both continuous CCP score [hazard ratio (HR) 1.373 per unit score, 95% confidence interval (CI) 1.006–1.874; p = 0.046) and the categorized CCP score (p < 0.001)were independent predictors of BCR. Conclusions: The present study provides insights into the role the CCP score plays in risk stratification of this cohort and in determining candidacy for deferred secondary treatment. From our perspective, the CCP score allows better stratification and can help identifying patients at lower risk of disease recurrence who could benefit from a wait-and-see policy. [ABSTRACT FROM AUTHOR]

Microphthalmia-associated transcription factor (MITF) is a key regulator for the development and function of melanocytes in skin, eye, and plumage pigmentations. Thus, the MITF was selected as a candidate gene associated with plumage coloration in ducks. This study analyzed the mRNA expression, promoter methylation, and polymorphisms in the MITF gene in ducks with different plumage colors (Putian Black, Putian White, Liancheng White, and Longsheng Jade-green). No expression of the MITF melanin-specific isoform (MITF-M) was detected in white feather bulbs. By contrast, the mRNA expression levels of MITF-M were high in black feather bulbs. Bioinformatics analysis showed that two CpG islands were present in the promoter region of the MITF gene. The methylation level of the second CpG island was significantly lower in black feather bulbs than in white feather bulbs. However, the methylation level of the first CpG island was not different among the feather bulbs with various colors except Liancheng White feather bulbs. The methylation status of the whole CpG island significantly and negatively correlated with the mRNA expression of MITF-M (P<0.05). Furthermore, four novel SNPs (single nucleotide polymorphisms) were identified in the 5′UTR, exon 4, intron 7, and intron 8 of the MITF gene. Allele T in g.39807T>G and allele G in g.40862G>A were the predominant alleles only found in Putian White, whereas the variant A allele in g.32813G>A exhibited a high allele frequency in Liancheng White. Collectively, these results contributed to the understanding of the function of the MITF gene in duck plumage coloration. [ABSTRACT FROM AUTHOR]

[Display omitted] • The molecular differences in serum between benign prostatic hyperplasia and prostate cancer can be detected by Surface-enhanced Raman Spectroscopy (SERS) accurately. • Applying the Convolutional Neural Network (CNN) to Surface-enhanced Raman Spectroscopy (SERS) data analysis makes extraction of valid information comprehensive and efficient. • Introduction of age and PSA into SERS-based CNN model makes classification of benign and malignant more accurate. • This is a large sample study with total 2187 SERS spectra from 729 patients. We collected surface-enhanced Raman spectroscopy (SERS) data from the serum of 729 patients with prostate cancer or benign prostatic hyperplasia (BPH), corresponding to their pathological results, and built an artificial intelligence-assisted diagnosis model based on a convolutional neural network (CNN). We then evaluated its value in diagnosing prostate cancer and predicting the Gleason score (GS) using a simple cross-validation method. Our CNN model based on the spectral data for prostate cancer diagnosis revealed an accuracy of 85.14 ± 0.39%. After adjusting the model with patient age and prostate specific antigen (PSA), the accuracy of the multimodal CNN was up to 88.55 ± 0.66%. Our multimodal CNN for distinguishing low-GS/high-GS and GS = 3 + 3/GS = 3 + 4 revealed accuracies of 68 ± 0.58% and 77 ± 0.52%, respectively. [ABSTRACT FROM AUTHOR]

Objective To determine the prognostic utility of serum chromogranin A (CgA) and neurone-specific enolase ( NSE) variations during the first 3 months of abiraterone acetate ( AA) treatment in patients with metastatic castration-resistant prostate cancer ( mCRPC). Patients and Methods The serum levels of CgA, NSE were measured at baseline and after 3 months of AA treatment in 40 patients with mCRPC. Outcome measures were prostate-specific antigen progression-free survival ( PSA- PFS), radiographic PFS ( rPFS), and overall survival ( OS). Results CgA levels were not correlated with NSE levels ( P = 0.296). In multivariate analysis the combination of CgA and NSE (≥1 marker positive vs both markers negative) and the combination of CgA and NSE elevation during the first 3 months of AA treatment (≥1 marker positive vs both markers negative) remained significant predictors of OS, rPFS, and PSA- PFS. Conclusion We found that CgA and NSE elevation during the first 3 months of AA treatment and elevated baseline CgA and NSE levels were independent prognostic factors for OS, rPFS and PSA- PFS in patients with mCRPC treated with AA. This suggests that serial CgA and NSE evaluation may help clinicians in distinguishing patients with mCRPC who would obtain the best survival benefit from AA treatment. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate and compare the efficacy of prostate volume (PV), transitional zone volume (TZV), and prostate volume index (PVI, the ratio of TZV to peripheral zone volume) in the identification of men at risk of prostate cancer (PCa) and high-progression PCa (HPPCa) at the initial biopsy (IBX) in a real-world population. Methods: From Jul 2014 to Aug 2016, data on 1144 patients who had undergone the initial prostate biopsies were prospectively collected and analyzed. Univariate and multivariate logistic regression analyses were performed to identify the independent predictors for PCa and HPPCa. Based on independent predictors, nomogram models were developed and internally validated to assess a man's risk of harboring PCa and HPPCa. Results: The detection rates of PCa and HPPCa were 43.09% (493/1144) and 39.16% (448/1144), respectively. In the multivariate analyses, age, PSA, TZV, DRE, and TRUS instead of PV or PVI were independent predictors for PCa and HPPCa, percent free PSA was independent predictor for PCa not for HPPCa. Such independent predictors were finally included in the nomogram models. The AUCs of TZV-based nomogram models were 87.0% for PCa and 87.7% for HPPCa, which were higher than that of PSA alone or other predictive models. Conclusions: TZV is a better predictive biomarker than PV or PVI for PCa and HPPCa, we recommend adding TZV but not PV or PVI to the nomogram models to improve the predictive accuracy of PCa and HPPCa at IBX. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the ability of the new Gleason grade groups (GGGs) to stratify risk in prostate cancer patients with locally adverse pathologic features after radical prostatectomy (RP) thereby allowing more accurate assessment for planning eventual adjuvant therapy. Patients and methods: Data on 172 patients with locally adverse pathologic features (including seminal vesicle invasion, extracapsular extension, or positive surgical margins) who had been treated with wait and see policy after RP were retrospectively analyzed for biochemical recurrence (BCR)-free survival. Kaplan-Meier survival analysis and Cox proportional hazard regression models were used to test the association between the GGGs and BCR. Finally, concordance indices of different grading classifications were calculated to evaluate the predictive accuracy for biochemical failure after RP. Results: The five-year BCR-free survival rates were 71.2, 66.9, 25.7, 17.4, and 8.3 % for GGG 1-5 assessed on surgical specimens ( p < 0.001, log-rank test). In the two-way log-rank test, men with prostatectomy GGG 2 had a lower progression risk relative to GGG 3 ( p = 0.001), though similar risk as GGG 1 ( p = 0.105). In multivariate Cox regression analysis, specimen GGG ≥3 and early postoperative PSA ≥0.1 ng/ml were independent risk factors for biochemical failure ( p < 0.001). In addition, GGGs had higher predictive accuracy compared with the alternate classification system (improvement in concordance index by 0.036-0.141). Conclusions: For the appropriate patient, depending on age, physical condition, early postoperative PSA, patient desire, etc., could be a candidate for wait and see policy with specimen GGG 2 disease, so to distinguish this from GGG 3 may facilitate discussions at the point of treatment decision making. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) incidence and mortality have rapidly increased in China. Notably, unique epidemiological characteristics of PCa are found in the Chinese PCa population, including a low but rising incidence and an inferior but improving disease prognosis. Consequently, the current treatment landscape of PCa in China demonstrates distinct features. Establishing a more thorough understanding of the characteristics of Chinese patients may help provide novel insights into potential treatment strategies for PCa patients. Herein, we review the epidemiological status and differences in treatment modalities of Chinese PCa patients. In addition, we discuss the underlying socioeconomic and biological factors that contribute to such diversity and further propose directions for future efforts in optimizing the PCa treatment in China. [ABSTRACT FROM AUTHOR]

In urogenital cancers, few reliable biomarkers have been established to deliver precise cancer detection in a non-invasive way. Extracellular vesicles (EVs) with rich cancer specific biocomponents can provide tumor trails and serve as a novel biomarker. Surface-enhanced Raman Spectroscopy (SERS) analysis of serum-derived EVs combined with deep learning algorithms shows high accuracies in diagnosis of three common urologic cancer in clinical cohorts, providing a novel tool in non-invasive cancer detection. [Display omitted] • Diagnostic tools for urologic cancers are invasive with high negative rates and complications. • Extracellular vesicles (EV) are broadly involved in urologic cancer development and progression. • Surface-enhanced Raman Spectroscopy (SERS) can analyze EV rapidly and accurately in a label-free manner. • Deep learning based SERS analysis of EV achieve high accuracies in urologic cancer diagnosis. • SERS analysis of serum-derived EV is superior than serum in urologic cancer diagnosis. To identify and compare the capacities of serum and serum-derived small extracellular vesicles (EV) in diagnosis of common urogenital cancer combining Surface-enhanced Raman spectroscopy (SERS) and Convolutional Neural Networks (CNN). We collected serum samples from 32 patients with prostate cancer (PCa), 33 patients with renal cell cancer (RCC) and 30 patients with bladder cancer (BCa) as well as 35 healthy control (HC), which were thereafter used to enrich extracellular vesicles by ultracentrifuge. Label-free SERS was utilized to collect Raman spectra from serum and matched EV samples. We constructed CNN models to process SERS data for classification of malignant patients and healthy controls (HCs). We collected 650 and 1206 spectra from serum and serum-derived EV, respectively. CNN models of EV spectra revealed high testing accuracies of 79.3%, 78.7% and 74.2% in diagnosis of PCa, RCC and BCa, respectively. In comparison, serum SERS-based CNN model had testing accuracies of 73.0%, 71.1%, 69.2% in PCa, RCC and BCa, respectively. Moreover, CNN models based on EV SERS data show significantly higher diagnostic capacities than matched serum CNN models with the area under curve (AUC) of 0.80, 0.88 and 0.74 in diagnosis of PCa, RCC and BCa, respectively. Deep learning-based SERS analysis of EV has great potentials in diagnosis of urologic cancer outperforming serum SERS analysis, providing a novel tool in cancer screening. [ABSTRACT FROM AUTHOR]

Background: Platelet to Lymphocyte ratio (PLR) is thought to be associated with a worse outcome in multiple types of cancer. However, the prognostic significance of PLR has not been investigated in the prostate cancer (PCa) patients receiving hormonal therapy. The objective of this study was to determine the prognostic value of PLR in PCa patients treated with androgen deprivation therapy (ADT).Methods: Two-hundred-ninety prostate cancer patients who had undergone ADT as first-line therapy were retrospectively analyzed. The blood cell counts were performed at the time of diagnosis. PLR was calculated as the ratio of platelet count to lymphocyte count. Patients were categorized in two groups using a cut-off point of 117.58 as calculated by the receiver-operating curve analysis. Correlations between PLR and clinical characteristics were analyzed. Meanwhile, univariate and multivariate cox regression analyses were performed to determine the associations of PLR with progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Prognostic accuracy was evaluated with the Harrell concordance index.Results: The differences of age, serum prostate-specific antigen (PSA) level, Gleason score, risk stratification and incidence of metastasis between low PLR group (<117.58) and high PLR group (≥117.58) were not statistically significant (p > 0.05). Multivariate analyses identified PLR as an independent prognostic factor for PFS (hazard ratio (HR) = 1.581, p = 0.013), CSS (HR = 1.768, p = 0.037) and OS (HR = 1.650, p = 0.044). The addition of PLR to the final model improved predictive accuracy (c-index: 0.747, 0.801 and 0.768) for PFS, CSS and OS compared with the clinicopathological base model (c-index: 0.730, 0.778 and 0.746), which included Gleason score and incidence of metastasis.Conclusions: PLR might play a significant role in the prognosis of PCa patients treated with ADT. Thus, we recommend adding PLR to traditional prognostic model to improve the predictive accuracy. [ABSTRACT FROM AUTHOR]

With the advantages of avoiding land-use competition, biomass from agricultural residues is a promising solution to alleviate the energy crisis and environmental problems. In the traditional biomass utilization management problem, few studies have considered that land and water are key resources for the sustainable development of biomass from a life cycle view. Concerning the complex food-water-energy nexus, this paper focuses on the synergetic management of crop planting structure and biomass utilization as a whole system. An integrated framework is proposed for the co-optimization of cropland distribution and biomass utilization pathway under multiple uncertainties. Base on interval programming and fuzzy set theory, a type-2 fuzzy interval linear programming model is developed to handle multiple uncertainties with various characteristics and provide the optimum strategies for decision makers with different risk preferences. The proposed framework is verified by a case study of Hebei Province, China. Moreover, the impacts of water shortage and the implementation of the carbon price on the optimized strategies, economic and environmental benefits are investigated to provide deeper management insights when facing complex external factors. The obtained results suggest that corn and wheat will still be the primary crops, and bioethanol production will gain priority in the biomass utilization pathways for economic purposes. Water resources availability will greatly affect the crop planting allocation as well as total benefits but barely influence the biomass utilization pathways. Furthermore, with the implementation of the carbon trade market, a higher carbon price will stimulate biomass pellets production to replace fossil fuel consumption and improve the economic benefits directly. • Synergetic management of crop planting and biomass utilization is proposed. • A novel hybrid inexact programming approach is developed to address uncertainties. • The impacts of water resources availability are analyzed from a nexus perspective. • The influences of carbon price on the biomass utilization pathway are explored. [ABSTRACT FROM AUTHOR]

Shanghai is a megacity located in a hazard-prone region, but one in which local residents have not actively engaged in disaster risk management. This paper aims to identify factors of perception that influence residents' propensity to adopt risk-mitigating measures. It presents results of a structured questionnaire survey administered to Shanghai residents. Results show that risk-mitigating measures are deemed to be important if people: (1) have frequently experienced extreme weather; (2) believe that extreme weather events are severe in Shanghai; and (3) are concerned about other public risks confronting international society, such as energy security and terrorism. It is important to note that the third point has resulted in greater impacts than the other two factors. A cultural explanation is offered in this paper. Public risk awareness emanates from a generic concern over the security of the human world. This generic concern acts as a socio-cultural backdrop that contextualises the ways in which individuals respond to natural hazards. The significance of this factor indicates the need for broadening the analytical scope of risk perception research in China. These findings are useful for local policymakers, emergency managers and community and aid organisations seeking to develop creative strategies for risk education and communication. [ABSTRACT FROM AUTHOR]